Action Points

Note that this small, randomized trial demonstrated that a personalized polypeptide vaccination was associated with increased overall survival in refractory bladder cancer.

Be aware that this outcome was not the prespecified primary endpoint of the study.

Adding a "personalized peptide vaccine" (PPV) to best supportive care improved overall survival in patients with bladder cancer that progressed after a platinum-based chemotherapy regimen, a small randomized trial in Japan showed.

In a cohort of 80 patients with progressive bladder cancer following first-line treatment with platinum drugs, median overall survival was 7.9 months for those randomized to receive PPV plus best supportive care compared with 4.1 months in those only receiving supportive care (P=0.049), according to Masanori Noguchi, MD, of Kurume University School of Medicine in Japan, and colleagues writing in Clinical Cancer Research.

But there was no difference in progression-free survival (2.0 months with PPV vs 1.8 months with supportive care alone, P=0.17).

No immune-related serious adverse events were observed in patients who received the additional PPV strategy and treatment was extremely well tolerated.

The PPV used in the study was created individually for each patient, using HLA-matched peptides selected from a set of 31 on the basis of the patient's HLA type and "pre-existing host immunity," the researchers explained.

"To date, only a few pilot clinical trials have been conducted to evaluate vaccine candidates for bladder cancer and these trials were conducted on a limited number of study patients and only in the context of advanced invasive bladder cancer," they wrote.

"This study is, to our knowledge, the first randomized phase II study investigating the efficacy of PPV treatment in patients with metastatic bladder cancer after failure of platinum-based regimens and showed longer survival after cancer vaccination than best supportive care treatment."

Eligible patients had histologically proven metastatic urothelial carcinoma of the bladder and had progressed within 12 months after receiving first-line platinum based chemotherapy. Patients were also required to have measurable disease and a life expectancy of at least 12 weeks.

The mean number of courses of platinum-based chemotherapy received prior to enrolment was not different between the two treatment groups and all patients had clearly progressive disease and metastatic lesions within 1 year after receiving first-line chemotherapy.

Median duration of follow-up was 6.8 months (interquartile range 2.8-13.1) in the PPV plus best supportive care group and 3.2 months (IQR 1.5-7.3) in the best supportive care group.

At data cut-off (April 20, 2014) almost three-quarters of patients overall had died from their disease. However, risk of death was reduced by 42% in the experimental arm compared with the control arm at a HR of 0.58 (95% CI 0.34-0.99; P=0.049).

Noguchi and colleagues found that that the onset of clinical benefit from the PPV strategy was slow, with both overall and progression-free survival curves diverging between the two arms relatively late in follow-up. Indeed, some patients randomized to additional PPV initially experienced disease progression following randomization.

In contrast to chemotherapy or small molecules, PPV may take time to induce an effective immune response, Noguchi and colleagues suggested.

Delayed clinical benefit has also been noted for other immunotherapeutic approaches such as ipilimumab and sipuleucel-T.

Limitations of the study include the fact that investigators failed to detect a significant difference in progression-free survival which they speculate might be due to the small sample size.

The study was also unblinded and 20% of randomized patients did not receive treatment.

Due to these limitations, investigators are currently preparing to conduct a larger scale double-blind placebo-controlled randomized trial in the second-line setting.

Dan Petrylak, MD, professor of medicine and director of the genitourinary translational research group at Yale University, told MedPage Today that immunotherapies clearly can work in metastatic bladder cancer, as shown by the success of anti-CTLA-4 antibody therapies such as ipilimumab (Yervoy).

"There's clearly activity with this approach and it doesn't surprise me that a vaccine that is personalized is showing activity as well," Petrylak said

"So it's a new era as far as treatment of bladder cancer is concerned and now the question is: How do we sequence these new therapies and how do we use them?"

MedPageToday is a trusted and reliable source for clinical and policy coverage that directly affects the lives and practices of health care professionals.

Physicians and other healthcare professionals may also receive Continuing Medical Education (CME) and Continuing Education (CE) credits at no cost for participating in MedPage Today-hosted educational activities.